Neurobehavioral and fMRI Research in HIV Infection and Cocaine Dependence Dr. Christina Meade's long-term goal is to establish an independent and productive program of patient-oriented research dedicated to understanding the impact of drug abuse on behavioral and clinical outcomes in persons living with or at risk for HIV/AIDS. This application presents integrated training and research plans focused on HIV neurobehavioral dysfunction. The guiding hypothesis is that co-occurring HIV infection and cocaine dependence is associated with greater neurocognitive impairment and behavioral risk compared to each disease independently. As the fields of HIV/AIDS and drug abuse evolve, transdisciplinary research has the potential to accelerate advances in the prevention and treatment of these neuropsychiatric diseases. Therefore, Dr. Meade, a licensed clinical psychologist with a strong behavioral science background in HIV/AIDS and drug abuse, aims to develop expertise in cognitive neuroscience. Specifically, she seeks advanced training in: (1) neuroAIDS and neurocognitive assessment;(2) functional magnetic resonance imaging (fMRI);(3) brain circuitry relevant to addiction and neuroAIDS;and (4) longitudinal data analysis with repeated measures and latent variables. The training plan includes didactic coursework and workshops, one- on-one mentorship, participation in working groups and seminars, and attendance at national and international conferences. Consistent with the transdisciplinary nature of the proposed research, a mentorship team with distinct but complementary areas of expertise has been assembled: Drs. Scott Huettel (fMRI and executive function), Kevin Robertson (neuroAIDS and neuropsychology), Joseph McClernon (addiction and neuroimaging), Kathleen Sikkema (behavioral aspects of HIV), Rick Hoyle (statistics and methodology), and Roger Weiss (drug addiction). Duke University provides a rich environment in which Dr. Meade's career development goals can be readily accomplished, including access to state-of-the-art neuroimaging facilities, clinical units supportive of patient-oriented research, graduate-level courses in fMRI, statistics, and neurobiology, and several directly relevant interdisciplinary research centers and institutes. The research plan has been carefully designed to parallel the training plan;for each training goal there is a corresponding research directive that will allow Dr. Meade to implement newly developed skills. Both HIV infection and stimulant abuse affect neurocognitive functioning, yet few studies have empirically examined the effects of co- occurring HIV infection and stimulant abuse on neurobehavioral outcomes. This is an important research topic due to the high prevalence of co-occurring HIV infection and stimulant abuse, and the high rates of risky and impulsive behavior in this population. The research plan has 2 studies with the following specific aims: (1) identify patterns of neurocognitive impairment in HIV infection and cocaine dependence, and test whether these are associated with risky decision making and behavioral risk;and (2) examine brain activation patterns associated with attention and decision making as a function of HIV disease progression and co-occurring versus independent HIV infection and cocaine dependence. A sample of 160 patients will be recruited for a 3- group comparison study of persons with co-occurring HIV infection and cocaine dependence, HIV infection only, and cocaine dependence only. Participants will complete a battery of neurocognitive and behavioral measures;results will be analyzed using latent variable techniques. A subset (25 from each group, 75 total) will participate in an fMRI experiment that examines brain activity during attention and decision tasks;within and between group analyses will be conducted. This integration of behavioral and cognitive neuroscience techniques is novel and innovative, and results may help shed light on the mechanisms underlying neuropsychiatric disorders characterized by risk taking and impulsivity. This line of research has the potential to improve techniques for early identification of neurocognitive impairment and guide the development of transformative treatment approaches to improve behavioral and clinical outcomes in this population. Moreover, as a clinician, Dr. Meade will be uniquely poised to translate these findings into clinical practice. In sum, the proposed K23 award will provide the advanced training and mentored research necessary for Dr. Meade to become a nationally recognized expert in the neuropsychiatry of drug abuse and HIV/AIDS and to conduct transdisciplinary research in this evolving field. PUBLIC HEALTH RELEVANCE: Over 1 million Americans are living with HIV/AIDS, with approximately 56,000 new infections each year in the United States. Stimulant abuse, primarily cocaine and methamphetamine, is common among HIV-infected adults and is associated with continued sexual risk taking, poor treatment adherence, and other risky behaviors. A better understanding of the underlying mechanisms associated with neurobehavioral dysfunction in HIV-infected drug abusers may guide the development of innovative prevention and treatment approaches.